Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 1;8(8):e2525252.
doi: 10.1001/jamanetworkopen.2025.25252.

Antibiotic Use and the Risk of Hospital-Onset Clostridioides Difficile Infection

Mayan Gilboa  1   2   3 , Gili Regev-Yochay  1   2   3 , Eyal Meltzer  1   4 , Ido Cohen  1   5 , Yovel Peretz  2   3 , Tal Zilberman-Daniels  1   6   7 , Amitai Segev  1   8 , Sharon Amit  1   6 , Dafna Yahav  1   7 , Noam Barda  2   9   10   11
Affiliations

Antibiotic Use and the Risk of Hospital-Onset Clostridioides Difficile Infection

Mayan Gilboa et al. JAMA Netw Open. .

Abstract

Importance: Clostridioides difficile is a leading cause of health care-associated infections. Understanding the association among C difficile carriage, antibiotic use, and infection hazard is essential for infection prevention.

Objective: To evaluate the hazard of C difficile infection (CDI) among asymptomatic carriers vs noncarriers of C difficile and whether it is associated with antibiotic exposure.

Design, setting, and participants: This retrospective cohort study conducted between June 18, 2017, and June 21, 2023, analyzed hospitalizations from Sheba Medical Center in Ramat Gan, Israel, which routinely screens for C difficile in high-risk patients admitted to internal medicine. Adult patients (aged >18 years) without active CDI at admission were included.

Exposure: Antibiotic exposure during hospitalization, including specific classes.

Main outcomes and measures: The primary outcome was the development of CDI, as confirmed by laboratory testing for C difficile. Antibiotic exposure was assessed as a time-varying variable.

Results: The study included 33 756 hospitalizations among 23 001 patients (median [IQR] age, 78 [68-87] years; 52.8% men). C difficile infection occurred in 67 of 1624 hospitalizations (4.1%) with positive screening results and in 47 of 32 132 hospitalizations (0.1%) with negative screening results. A positive C difficile screening result at admission was associated with a high hazard of infection (hazard ratio [HR], 27.5; 95% CI, 18.7-40.3). Antibiotic exposure was associated with an increased hazard for CDI (HR, 1.98; 95% CI, 1.24-3.16). Piperacillin and tazobactam showed the most pronounced hazard for CDI (HR, 2.18; 95% CI, 1.41-3.36). Among asymptomatic carriers, antibiotic exposure was not significantly associated with a further increase in CDI hazard (HR, 1.07; 95% CI, 0.73-1.58).

Conclusions and relevance: In this cohort study, carriers of C difficile had a substantially higher baseline hazard for hospital-onset CDI. Antibiotic exposure was associated with an increased hazard among noncarriers but was not significantly associated with additional hazard among carriers. These findings suggest that while antibiotic stewardship may reduce CDI risk in noncarriers, additional strategies may be needed for carriers given their elevated baseline risk.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Prof Regev-Yochay reported receiving grants from Pfizer and Moderna and advisory board fees from GlaxoSmithKline and MSD outside the submitted work. Prof Yahav reported collaboration on a Pfizer-sponsored study and receiving grants to her institution from Shionogi outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Population Flowchart
CDI indicates Clostridioides difficile infection; ICU, intensive care unit; LOS, length of stay. aSpecific CDI definition is positive polymerase chain reaction and enzyme immunoassay results for C difficile toxin.
Figure 2.
Figure 2.. Flexible Modeling of the Association Between Days of Treatment With Any Antibiotic and Clostridioides Difficile Infection (CDI)
Hazard ratios were estimated using Cox models adjusted for age, sex, Charlson Comorbidity Index score, functional status, immunosuppression, and protein pump inhibitor use. Associations were modeled using restricted cubic splines. Shading indicates the 95% CI.
See this image and copyright information in PMC

References

    1. Linsenmeyer K, O’Brien W, Brecher SM, et al. Clostridium difficile screening for colonization during an outbreak setting. Clin Infect Dis. 2018;67(12):1912-1914. doi: 10.1093/cid/ciy455 - DOI - PubMed
    1. Magill SS, Edwards JR, Bamberg W, et al. ; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team . Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198-1208. doi: 10.1056/NEJMoa1306801 - DOI - PMC - PubMed
    1. Lanzas C, Dubberke ER, Lu Z, Reske KA, Gröhn YT. Epidemiological model for Clostridium difficile transmission in healthcare settings. Infect Control Hosp Epidemiol. 2011;32(6):553-561. doi: 10.1086/660013 - DOI - PMC - PubMed
    1. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(suppl 2):S88-S92. doi: 10.1093/cid/cis335 - DOI - PMC - PubMed
    1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825-834. doi: 10.1056/NEJMoa1408913 - DOI - PMC - PubMed

Substances

LinkOut - more resources